Activation of ERK/MAPK in the lateral amygdala of the mouse is required for acquisition of a fear-potentiated startle response.

There is considerable interest in examining the genes that may contribute to anxiety. We examined the function of ERK/MAPK in the acquisition of conditioned fear, as measured by fear-potentiated startle (FPS) in mice as a model for anticipatory anxiety in humans. We characterized the following for the first time in the mouse: (1) the expression of the ERK/MAPK signaling pathway components at the protein level in the lateral amygdala (LA); (2) the time course of activation of phospho-activated MAPK in the LA after fear conditioning; (3) if pharmacological inhibition of pMAPK could modulate the acquisition of FPS; (4) the cell-type specificity of pMAPK in the LA after fear conditioning. Using western blot and immunohistochemistry techniques and injecting the MEK inhibitor U0126 in the LA, we showed the following: (1) both MEK1/MEK2 and ERK1/ERK2 were co-expressed in the LA of the adult mouse brain; (2) there is a peak of pMAPK at 60 min after fear conditioning; (3) the ERK/MAPK signaling pathway activation is essential for the acquisition of an FPS response; (4) at 60 min, the pMAPK are exclusively neuronal and not glial. These results emphasize the importance of this signaling pathway in the acquisition of conditioned fear in the mouse. Given the widely held view that conditioned fear models the essential aspects of anxiety disorders, the results confirm the ERK/MAPK signaling pathway as a molecular target for the treatment of anxiety disorders in the clinic

Neuroimaging Studies of Emotional Responses in PTSD

Neuroimaging research offers a powerful and noninvasive means to understand healthy as well as dysregulated emotional processing in healthy subjects and PTSD patients. Functional neuroimaging findings suggest specific roles for subregions of the medial prefrontal (mPFC), orbito frontal (OFC), anterior cingulate (ACC), and insular cortices as well as the sublenticular extended amygdala (SLEA) and hippocampus in various components of emotional processing. Some of the same regions appear to be associated with emotional response to trauma, and with symptom formation in PTSD. Neuroimaging findings of emotional processing in healthy subjects and PTSD patients are discussed, addressing the specific roles of cortical regions like mPFC, ACC, and insula, and their potential contribution to PTSD pathophysiology. Processes of cognitive–emotional interactions and social emotions are discussed in an attempt to synthesize the prefrontal findings in healthy subjects and PTSD patients. Further links between functional neuroanatomy of emotional responses and neuroendocrine stress regulation are proposed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74195/1/annals.1364.009.pd